Knee Pain Top of Kneecap

Knee pain at the top of the knee cap (knee pain top of kneecap) can be caused by an alignment problem, cartilage injury, patellar tendon issues, or trigger points in the quadriceps muscle. The knee cap fits into a groove in the end of the femur (thigh bone). When the muscle that controls the knee cap (quadriceps) pulls on one side of the knee cap more than the other, the knee cap can get out of alignment. This is discussed further in our book on new approaches to orthopedic problems and stem cells. As the knee cap travels through it’s groove, the cartilage on the back of the knee cap and on the femur help to make the knee cap glide smoothly. When this cartilage gets injured or has been worn away through arthritis, knee pain at the top of the knee cap can be the result. The knee cap lives in a tendon (the end of the quadriceps muscle) that anchors itself to the leg bone (tibia). This whole mechanism (muscle, knee cap, and tendon) move the leg bone forward when you kick, run, or walk. When the muscle has areas that are shut down due to nerve issues in the back, the tendon can be pulled on too much, leading to pain at the top of the knee cap. In addition, the tendon can become injured by trauma such as kicking into turf. Finally, the quadriceps muscle itself may be the problem. The muscle can develop trigger points (as discussed above) which can cause pain and weakness in the muscle. These trigger points can refer knee pain to the top of the knee cap. If you have any of the problems causing knee pain at the top of the kneecap, what can you do? If the knee cap isn’t well aligned, there are many types of physical therapy that can help that alignment (see our book on new biologic orthopedic techniques). Taping the knee cap may help in addition to these special exercises. If you have a cartilage injury or arthritis causing this knee pain, investigate whether stem cell injection options may help your pain. If the tendon is the problem we’ve had excellent results with platelet rich plasma or stem cell plasma injections into the tendon under imaging guidance. Also consider what biomechanical problems might be causing too much pressure on the knee cap tendon. Finally, if the quadriceps muscle is the cause, IMS trigger point needling works well. In summary, knee pain at the top of the knee cap has a few causes, all of which are treatable.

Pudendal Nerve Entrapment and Pelvic Ligament Problems

 

RD is a middle-aged ex-fireman who injured his hip and sacro-iliac joint in a fall. We treated his pain with SI joint injections and epidurals, but recently he began to talk about sexual dysfunction. He consulted multiple specialists without any answers. He finally asked me if it could be due to his back. His MRI showed no severe issues that could cause sexual dysfunction, so we began looking for other sources. In particular, he was very tender over the sacrospinous ligament, which travels from the bottom of the tailbone (sacrum) to the bottom part of the pelvic bone. Once I looked it up, it became clear that the pudendal nerve (that supplies the penis) travels under this ligament (ligament in red above, star shape at site where nerve gets entrapped). It was worth a shot (literally) as he had no other options and cutting the ligament would destabilize his pelvis and SI joint complex. Under ultrasound guidance we localized his sacrospinous ligament and injected a small amount of anti-inflammatory. When I saw him two weeks later, his sexual dysfunction was gone, meaning that it’s likely the nerve was getting entrapped. While this may be a rare problem, the solution in this one patient was simple.

Ehler Danlos Syndrome Treatment

While we have seen a few patients through the years with Ehler Danlos Syndrome (EDS) variants or simply hypermobile tissue (patients that have very loose joints) without a confirmed diagnosis, I recently was asked by a severe EDS patient to consider prolotherapy for her frequently dislocating joints. EDS is a disease where the collagen (the stuff that holds our joints together) isn’t normal and is made by the body much too stretchy (see above picture). In it’s most severe forms, these patients can barely walk or be active without dislocating a joint. They tend to have arthritis at an early age due to the extra motion in their joints. This patient was in her early 20’s and unable to walk more than 20 steps without her left hip dislocating. She wore special rings on her fingers just to keep her finger joints from poping out of place. She wanted to try prolotherapy on the theory that it would beef up her already loose tissue, laying down thicker tissue or more of the same stretchy stuff, but maybe enough to keep her joints more in place. I was skeptical, but she had no other options. I’m happy to say that after several x-ray guided prolotherapy injections in her left hip and the surrounding tendons she now reports that she can walk through a home depot without the need for her scooter and has had a record low number of hip dislocations this past month. The theory here seems to be correct, that in severe EDS patients injecting substances that have been shown to “beef-up” tissue may give them anough added stability to function better.

Steroids and Apoptosis

Apoptosis means pre-programmed cell death.  High dose steroids (corticosteroids which are commonly used to decrease swelling) have been implicated in causing this condition.  When I first heard about this issue from chiropractors and physical therapists years ago, I though it was an alternative medicine marketing tactic.  However, as I read more, it became clear that these negative effects of steroids on muscles, bones, cartilage, and ligament were quite real.  I have summarized those here:

–Cartilage

–Muscle

-Bone

-Ligament

An upper back problem that looks like it’s abdominal pain…

Jimmy was a teenage baseball player with a history of severe abdominal pain.  I think his case illustrates how many M.D.’s have lost our ability to structurally diagnose patients with chronic pain.  Since he had high abdominal pain below the ribs, he had the million dollar GI work-up for his abdominal pain.  He was ultimately placed on very high dose narcotics and other drugs by a local Childern’s hospital.  When he first came to our clinic, his pain was across the top of his stomach and he couldn’t sleep more than 1-2 hours a night.  He wasn’t eating well and had given up baseball (his passion).  What was striking on initial exam was that if this patient had an internal organ problem, you wouldn’t expect his upper abdomen to be tender, right along the rib cage.  When these lower ribs were followed to his upper back, he had muscle spasms in this area as well.  Since nobody had ever found anything wrong with little Jimmy’s internal organs, it was a safe bet that he had a lower thoracic problem leading to pain in the ribs, which masqueraded as a stomach problem.  Further exam in Jimmy’s case showed that the abdominal muscles had significant trigger points and the area that attached to the ribs had a significant enthesopathy (swelling at the tendons that attach to bone, due to excessive pulling on the attachment by tight muscles).  Our plan was to begin injecting the lower ribs with prolotherapy solution to allow these abdominal muscle attachments to heal and to get rid of trigger points in the abdominal and upper back muscles using an IMS technique.  Within 12 weeks (Jimmy had suffered for two years), Jimmy was back to playing baseball and without pain.  He went off all meds and at one year follow-up, he’s still off meds and without pain.  His case is a good example of how a simple musculosketal pain problem can be misdiagnosed, cost a bunch of money in expensive diagnostic work-up, and if undiagnosed and without proper treatment, would have led to a teenager addicted to narcotics.

Can stem cells fix a knee?

Cartilage is funny stuff.  It’s a shock absorber and filled with cells, so it’s alive.  For a long time, we doctors believed is was so much inert filler so we developed a surgical culture of trimming it and cutting it out.  This was called debridement.  The problem is that arthoscopic surgery for knee pain doesn’t work.  The reason, cutting out living cells turns out to be a bad idea.  So the next step is actually trying to fix cartilage.  We have demonstrated on MRI that using the patient’s own stem cells can help the appearance of knee cartilage (as seen on high resolution MRI) as well as the pain reported by patients.  The secret appears to be taking the patient’s own stem cells and growing them to bigger numbers.  The FDA has taken a strange position on all of this, but doctors and patients have other ideas.  In the meantime, fixing cartilage with stem cells seems like a better idea than cutting it out.

New Physician Group Releases Lab Guidelines for Safe Stem Cell Therapy

The American Stem Cell Therapy Association (ASCTA) announced this week the publication of their lab guidelines.  The group of physicians have come together to oppose the FDA’s position that the patient’s own adult stem cells are drugs.  Why is this important?  The FDA’s believes that classifying adult stem cells as drugs will improve safety.  However, many of the drug manufacturing guidelines don’t apply to the processing of a patient’s own cellular material, a bit like trying a force square peg in a round hole.  ASCTA has put together lab guidelines that will allow for lab safety that is much more specific to adult stem cells.  The first US lab to adopt these new guidelines will be the Regenexx lab in Colorado.  I was privileged to serve on the lab guidelines committee with noted scientists from various medical schools and biotech companies.

Patient Group Opposes FDA Position on Adult Stem Cells

Are your adult stem cells drugs?  The FDA has been sparring with physicians and patients over this issue.  Today a patient group registered it’s opposition to this FDA stem cell position.  For a real dose of reality about how good you have it, check out the “Patient Voices” section of this site.  These are people with terminal illness who are dying.  This whole debate started with the FDA’s position that the minimal stem cell culture process of the Regenexx procedure should be classified as a drug.  Why?  No real specifics give, it seems to be a “cause I said so” issue.  This lead to physicians organizing to regulate themselves so that patients can have access to safe adult stem cell therapy now.  Where is all of this going?  Adult stem cells processed with minimal culture techniques aren’t drugs, I suspect the best quote is from a physician from Ft. Meyers Florida who recently joined The American Stem Cell Therapy Association (ASCTA), “This is a patient physician situation and the FDA needs to stay out.  I commend all of you for starting this.”  Enough siad.

ISSCR Guidelines for Clinical Stem Cell Translation

As you may recall, the International Society of Stem Cell Researchers (ISSCR) released their new guidelines in response to many “off-shore” stem cell companies offering unknown origin “stem cells” to treat just about any illness. I was happy to see these guidelines. We think it’s important to compare the Regenexx Procedure to these guidelines. To make these easier to follow, the guidelines have been paraphrased.

• Stem cells from other people are more risky and need to be more closely monitored. The Regenexx procedure only uses autologous mesenchymal stem cells (MSC’s). This means that the stem cells that are used are only from the same patient. Research would suggest that stem cells from a donor may carry a genetic disease transmission risk. This means that cells from the bone marrow of another patient with osteoporosis may transmit that genetic disease to another patient.
• The use of animal components to grow cells must be replaced by human or non-animal components. Stem cells are commonly cultured in Fetal Calf Serum. With the infectious risks associated with FCS (for example, mad cow disease), FCS is not appropriate for human use. As a result, the Regenexx procedure (using a patent pending procedure) grows the patient’s stem cells in the natural growth factors obtained from the patient’s own blood platelets.
• Adverse changes to cells during culture must be minimized. In research, stem cells are often tricked into growing for extended periods. This can cause problems to develop in the cells, which can lead to the possibility of tumor formation. Extensive medical research has shown that MSC’s can be grown for about 5-6 weeks before they show signs of problems. We take a more conservative stance, that cells should only usually be grown for a maximum of 10-20 days.
• The level of oversight of stem cell therapy should be proportional to the risk. Stem cells from someone else’s body (allogeneic) should be scrutinized more closely than autologous (from the same person). Stem cells that are embryonic or cord blood in origin should also be considered to have more risk than adult stem cells. In addition, cells that are either heavily modified or manipulated (for example stem cells with changes to their genes) are more risky than cells that have been minimally manipulated. Finally, stem cells, which perform a certain function in the body, that are used to perform a different function in therapy (non-homologous) are more risky than homologous (stem cells that usually repair cartilage being used to repair cartilage). The Regenexx procedure takes the safest route on all of this issues-we use only autologous, adult origin, minimally manipulated, and homologous cells.
• Cells should be handled with adherence to set industry guidelines. The Regenexx procedure lab undergoes voluntary annual or biannual audits by Reglera, a leader in the cell culture standards industry. We follow all cGTP guidelines.
• Cell banking should have high standards. We offer patients the ability to freeze and store cells that are not being used for an active procedure. Rather than rely on the industry standard of liquid nitrogen storage, we have decided on the more expensive and higher standard of dry phase storage. Our rationale is that recent research questions whether viruses may be transmitted between patient’s samples via liquid nitrogen.
• Successful animal models are needed before stem cell therapy can be tried in humans. The Regenexx procedure uses only successful animal models before considering a treatment trial in human patients. For example, animal data must exist on the use of MSC’s for a specific application (like cartilage or tendon repair) before we will consider adding that disease to be treated. In addition, each new application for the procedure goes through a trial test period in an IRB approved study. Clinic physicians then use 3.0T MRI, exam, and patient reporting to decide if the procedure is working before releasing that treatment for commercial patients.
• Large animal models need to be used for tissue repair studies such as tendon, bone, or cartilage. Regenerative Sciences spent a year porting a large animal model treatment to a human model. The large animal model had proved successful before we considered moving the procedure to a human model.
• The cell line chosen for the therapy must first be shown not to be toxic or have adverse effects in the test tube or in animal models. We chose MSC’s because as of 2009 there are more than 7,000 published articles on this cell line. MSC’s are the most extensively researched of almost any stem cell line and known in animal models (as we deploy them) not to be toxic or associated with significant adverse outcomes.
• The risk of stem cell lines causing tumors must be accessed. We have already submitted early safety data for publication and maintain an extensive tracking database to rule out that stem cells from the Regenexx procedure are causing tumors. As of early 2009 this tracking database had 300 patients, with 600 expected by the end of 2009. No tumorogenicity has been observed.
• Animal models should exist which allow the clinician to determine the response of the stem cells to drugs the patient may be taking. The reason we chose the MSC stem cell line was the fact that so much data has been collected in animal models. We have many papers on the effects of everything from NSAID’s to obscure drugs on MSC’s. In addition, we have extensive clinical culture experience and have developed our own database of drugs that will reduce stem cell yield. Finally, we council our patients to get off of all possible prescription and non-prescription drugs prior to the procedure.
• All studies performed using stem cells should have a multidisciplinary review board to oversee human safety. The Regenexx procedure was developed under the auspices of a department of Health and Human Safety registered Institutional Review Board.
• The stem cell based therapy must offer a clinical advantage over existing therapies. The Regenexx procedure offers a lower risk option over traditional surgical options, which produce more tissue trauma, more downtime, more risk for infection or surgical adverse events.
• Patient monitoring and adverse event reporting are key components of stem cell therapy. As discussed above, we maintain a comprehensive complications and outcomes tracking database with regular patient contacts.
• The clinical outcomes (both good and bad) must be published in peer reviewed medical journals. We at RSI have already published imaging based case reports and are now moving onto clinical case series and safety studies. We are currently preparing for publication larger case series and will eventually move onto to randomized controlled placebo trials.

Bone Marrow Nucleated Cell Concentrate (BMAC): Is it Concentrated Enough?

 

bmac machine

 

In 2005-2006 we mixed up BMAC in our cell biology lab.  It was easy to create from a marrow aspirate.  We performed some basic MRI studies with pre and post 3.0T high field studies and ran outcome questionnaires for knee and hip arthritis patients.  We were unimpressed by the results and because of this experience moved on to culture expanded mesenchymal stem cells.  

 

BMAC has become popular of late. In this procedure, a physician takes a bone marrow aspirate, places it in a specially designed centrifuge and pulls out a concentrate of bone marrow nucleated cells. This has been billed as a stem cell concentrate, but the stem cells that are concentrated in reasonable numbers tend to be CD34+ heme progenitors (stem cells that make new blood) and not MSC’s (Mesenchymal Stem Cells). Since MSC’s are the MVP of the adult stem cell mix available in a bone marrow concentrate, their concentration is very important to the success of such a treatment. A recent study on bedside bone marrow concentrate machines for MSC’s (BMAC) determined what concentrations were possible from a commercially available centrifuge unit. Using this study to calculate MSC numbers, a 60 ml bone marrow draw would produce 70,000-90,000 MSC’s. The Regenexx procedure yields after culture expansion are in the 5M-100M range. Based on this data, the Regenexx procedure produces approximately 100-1,000 times more cells than you can obtain with BMAC bedside systems. Based on this and other data, our best estimate is that the average micro fracture procedure would release 5-10 ml of un-concentrated marrow, so about 500-1,000 MSC’s into the defect site. Our own dosing data and the copious animal research would suggest that for appropriate cartilage, tendon, ligament, muscle repair the necessary MSC dose is in the millions range. Obtaining that amount of MSC’s from a BMAC system would require unacceptably high volumes of whole marrow from the patient. The conclusion, while very convienent, BMAC doesn’t have the right stuff.

For more information on different stem cell types, I’ve posted a video below: